), and later updated in 1994 (2
), the Public Health Service (PHS) developedguidelines to identify persons at increased risk for HIV infection. These guidelines were published by the Centers for Disease Control and Prevention (CDC) and adopted by the OPTN to identify deceased organ donors at increased risk of infectious transmission. Currently, any donor falling into one or more of the 7 specified behavioral categories () is classified as a high risk donor (HRD) and subject to additional OPTN policies. Despite significant controversy surrounding their use, approximately 9% of donors where at least one organ is recovered are categorized as HRDs (3
Categories of behavior leading to classification of High Risk Donor
While the originally intended purpose of the HRD guidelines was to identify those at risk of prevalent infection, in practice this is not a relevant concern. UNOS mandates HIV and HCV antibody testing for all deceased donors and, as such, prevalent infections are detected (4
). However, no serologic test can detect infections that occurred very recently, so theconcern isincident infection occurring during the window period (WP), the time between acquisition of infection and serologic detectability. This scenario will likely result in a false-negative test result and transmission to the recipient(6
). As such, the HRD criteria are instead used as surrogate criteria to identify persons at risk of recently acquired infection
The PHS/CDC guidelines have not only been extrapolated in practice from prevalent HIV to WP incident HIV infection, but they have also been used as a default proxy for identifying deceased donors at risk for WP incident infections with hepatitis C virus (HCV)(9
).While HIV and HCV share several modes of transmission, their epidemiology is not identical. Both are blood-borne illness that can bespread parenterally(10
); however HCV transmission is thought to be more efficient by this route than HIV infection. Sexual transmission is considered one of the primary drivers of the HIV epidemic(12
); in contrast, sexual transmission of HCV is thought to be extremely inefficient, if at all relevant(13
).Several studies of HCV discordant couples found little to no evidence of sexual transmission(14
). Having multiple sexual partners may increase the risk of HCV infection(16
); however, it is unclear whether this is a real effect or the result of other confounding risk behaviors(18
).Three of the HRD categories are based on sexual behaviors (MSM, CSW, and high risk sexual behavior). It is unclear whether these categories are truly indicative of an increased risk for HCV.
An additional problem with expanding guidelines intended for HIV to HCV is that the two diseases have distinct clinical courses with different implications for serologic testing. While antibodies to HIV are typically produced within 3 weeks of infection (19
), HCV antibody formation does not occur for 8–12 weeks (20
), making the WP between acquisition of infection and serologic detectability by Enzyme-Linked Immuno- Assay (ELISA), an antibody-based method, much longer for HCV (approximately 66 days for HCV compared with 22 for HIV). Nucleic acid testing (NAT) is an alternative method based on detection of viral particles that shortens the WP to approximately 1 week (21
). While antibody testing is mandated for all donors (22
), the decision to use NAT is left to the individual Organ Procurement Organization (OPO). A survey of OPOs performed in 2008 found that 48.3% performed HCV NAT for all donors and an additional 20.7% performed it under certain circumstances (i.e. for HRDs only, when requested by the transplant center) (23
). NAT is not universally used because it is more expensive, time consuming, and thought to have a higher rate of false positives compared to ELISA (9
). However, given that HCV NAT decreases the WP by several months, the benefits for HCV detection may outweigh the risks in a more pronounced way than with HIV.
We hypothesized that the risk of HCV WP infection would be higher than the risk of HIV for some categories and significantly lower for others, and that quantifying these risks would be essential for informed clinical decision-making with regards to HRDs. The goals of our study were to (1
) estimate the incidence and variance of HCV infection within each category of HRD behavior, and (2
) estimate the risk of HCV WP infection, by ELISA and NAT, within each category of HRD behavior.